Opiates indications

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

Substitution therapy with methadone or buprenorphine has been veiy successfiil in terms of harm reduction. Some opiate addicts might also benefit from naltrexone treatment. One idea is that patients should undergo rapid opiate detoxification with naltrexone under anaesthesia, which then allows fiuther naltrexone treatment to reduce the likelihood of relapse. However, the mode of action of rapid opiate detoxification is obscure. Moreover, it can be a dangerous procedure and some studies now indicate that this procedure can induce even more severe and long-lasting withdrawal symptoms as well as no improvement in relapse rates than a regular detoxification and psychosocial relapse prevention program. 

Table 1 provides the urinalysis test results for the 4,847 arrestees, While PCP was tested for by an EMIT test only, cocaine, opiates and methadone were tested for by both EMIT and thin layer chromatography (TLC). (The EMIT test for opiates is not specific to morphine, the metabolite of heroin, and can detect the recent use of a variety of opiates. A specimen positive for opiates is most likely to indicate the use of heroin in this population, however.) Our analyses will use only the results from the EMIT tests, because we have learned that the TLC general drug screen is less sensitive for detecting recent use of these illicit street drugs (Wish et al. 1983 Wish et al. 1984). 

A test positive for opiates, cocaine, or methadone probably indicates that the drug was used within the prior 24 to 48 hours. 

Increasing evidence indicates that a chronic opiate-induced upregulation of the cAMP pathway, manifested by increased concentrations of adenylyl cyclase, PKA and several phosphoprotein substrates for the protein kinase, contributes to opiate tolerance, dependence and withdrawal exhibited by locus ceruleus neurons [66]. This upregulated cAMP pathway can be viewed as a homeostatic response of the neurons to persistent opiate inhibition of the cells. In the chronic opiate-treated state, the upregulated cAMP pathway helps return neuronal firing rates to control levels, i.e. tolerance. Upon abrupt removal of the opiate via the administration of an opiate receptor antagonist, the upregulated cAMP accounts for part of the withdrawal activation of the cells. 

Careful analyses of the pharmacologic properties of 3H-hailucinogen binding sites indicated that they may correspond to 5-HT receptors (in the case of 3H-LSD), sigma opiate receptors (in the case of 3H-PCP), or even GABA receptors (in the case of 3H-muscimol). Such data recall that hallucinogens should interfere markedly with the metabolism of neurotransmitters in the CNS. These hallucinogen-induced alterations of neurotransmitter metabolism and functions are summarized below. 

The cocaine addict most often presents during withdrawal after a binge of cocaine use. Cocaine withdrawal is not life threatening and does not require medical intervention in the same sense as alcohol or opiate withdrawal. It is, however, associated with a profound depression that can render the addict suicidal for 24-48 hours. The crashing cocaine addict should be assessed for suicide risk and, if indicated, the patient should be monitored in an emergency psychiatric setting or may require a brief 1-2 day inpatient psychiatric admission until the withdrawal resolves and the suicide risk is relieved. 

The main objective of this experiment was to demonstrate that a peptide lead compound could be used in rational design of a non-peptide library. One of the natural opiates, met-enkephalin, is used as a hypothetical lead compound. The averaged frequency distribution based on four SA runs is obtained (data not shown). Based on this result, 03 had the highest frequency, and the frequencies of A4, Dll, D13, D14, D16, D2, D3, D5, and D9 are also above random expectation. Apparently, 03 appeared in all the reported active peptoids with opioid activity (cf. Table 1). Comparison of the structure of met-enkephalin (Fig. 5) with 03 indicated that 03 is similar to the side chain of tyrosine, which is the N-terminal residue of met-enkephalin. Among other building blocks found more frequently than random expectation, A4, D3, and D13 are present in the reported opioid peptoids (cf. Table 1). Thus, the SA sampling correctly identified four... 

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